RESUMO
Clostridioides difficile typing is invaluable for the investigation of both institution-specific outbreaks as well as national surveillance. While the epidemic ribotype 027 (RT027) has received a significant amount of resources and attention, ribotype 106 (RT106) has become more prevalent throughout the past decade. The purpose of this systematic review was to comprehensively summarize the genetic determinants, antimicrobial susceptibility, epidemiology, and clinical outcomes of infection caused by RT106. A total of 68 articles published between 1999 and 2019 were identified as relevant to this review. Although initially identified in the United Kingdom in 1999, RT106 is now found worldwide and became the most prevalent strain in the United States in 2016. Current data indicate that RT106 harbors the tcdA and tcdB genes, lacks binary toxin genes, and does not contain any deletions in the tcdC gene, which differentiates it from other epidemic strains, including ribotypes 027 and 078. Interestingly, RT106 produces more spores than other strains, including RT027. Overall, RT106 is highly resistant to erythromycin, clindamycin, fluoroquinolones, and third-generation cephalosporins. However, the MIC90 in most studies are one to two fold dilutions below the epidemiologic cut-off values of metronidazole and vancomycin, suggesting both are acceptable treatment options from an in vitro perspective. The few clinical outcomes studies available concluded that RT106 causes less severe disease than RT027, but patients were significantly more likely to experience multiple CDI relapses when infected with a RT106 strain. Specific areas warranting future study include potential survival advantages provided by genetic elements as well as a more robust investigation of clinical outcomes associated with RT106.
Assuntos
Clostridioides difficile/classificação , Clostridioides difficile/genética , Infecções por Clostridium/microbiologia , Ribotipagem , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Clostridioides difficile/efeitos dos fármacos , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Genes Bacterianos , Humanos , Testes de Sensibilidade Microbiana , Vigilância em Saúde Pública , Ribotipagem/métodos , Esporos Bacterianos , VirulênciaRESUMO
Salmon recovery and the potential detrimental effects of dams on fish have been attracting national attention due to the environmental and economic implications. In recent years acoustic telemetry has been the primary method for studying salmon passage. However, the size of the existing transmitters limits the minimum size of fish that can be studied, introducing a bias to the study results. We developed the first acoustic fish transmitter that can be implanted by injection instead of surgery. The new injectable transmitter lasts four times longer and weighs 30% less than other transmitters. Because the new transmitter costs significantly less to use and may substantially reduce adverse effects of implantation and tag burden, it will allow for study of migration behavior and survival of species and sizes of fish that have never been studied before. The new technology will lead to critical information needed for salmon recovery and the development of fish-friendly hydroelectric systems.
Assuntos
Acústica/instrumentação , Salmão/fisiologia , Telemetria/instrumentação , Animais , Desenho de Equipamento , InjeçõesRESUMO
Acceleration in development of additional conventional hydropower requires tools and methods to perform laboratory and in-field validation of turbine performance and fish passage claims. The new-generation Sensor Fish has been developed with more capabilities to accommodate a wider range of users over a broader range of turbine designs and operating environments. It provides in situ measurements of three-dimensional (3D) linear accelerations, 3D rotational velocities, 3D orientation, pressure, and temperature at a sampling frequency of 2048 Hz. It also has an automatic floatation system and built-in radio-frequency transmitter for recovery. The relative errors of the pressure, acceleration, and rotational velocity were within ±2%, ±5%, and ±5%, respectively. The accuracy of orientation was within ±4° and accuracy of temperature was ±2 °C. The new-generation Sensor Fish is becoming a major technology and being deployed for evaluating the conditions for fish passage of turbines or other hydraulic structures in both the United States and several other countries.
RESUMO
The chromophore of the visual pigments, 11-cis retinal, is derived from vitamin A (all-trans retinol) through a series of reactions that take place in retinal pigment epithelium (RPE); (ref. 1). The first of these reactions is catalyzed by lecithin retinol acyltransferase (LRAT); (ref. 2). We screened 267 retinal dystrophy patients for mutations in LRAT and identified disease-associated mutations (S175R and 396delAA) in three individuals with severe, early-onset disease. We showed that the S175R mutant has no acyltransferase activity in transfected COS-7 cells. Our findings highlight the importance of genetic defects in vitamin A metabolism as causes of retinal dystrophies and extend prospects for retinoid replacement therapy in this group of diseases.
Assuntos
Aciltransferases/genética , Mutação , Degeneração Retiniana/genética , Aciltransferases/metabolismo , Idade de Início , Animais , Células COS , Membrana Celular/metabolismo , Feminino , Genes Recessivos , Humanos , Masculino , Repetições de Microssatélites , Mutação Puntual , Polimorfismo Conformacional de Fita SimplesRESUMO
Chronic treatment of BALB and GRS mice with BHT (2,6-di-tert-butyl-4-methylphenol) following a single urethane injection increases lung tumor multiplicity, but this does not occur in CXB4 mice. Previous data suggest that promotion requires the conversion of BHT to a tert-butyl-hydroxylated metabolite (BHTOH) in lung and the subsequent oxidation of this species to an electrophilic quinone methide. To obtain additional evidence for the importance of quinone methide formation, structural analogs that form less reactive quinone methides were tested and found to lack promoting activity in BHT-responsive mice. The possibility that promotion-unresponsive strains are unable to form BHTOH was tested by substituting this compound for BHT in the promotion protocol using CXB4 mice. No promotion occurred, and in-vitro work demonstrated that CXB4 mice are, in fact, capable of producing BHTOH and its quinone methide, albeit in smaller quantities. Incubations with BALB lung microsomes and radiolabeled substrates confirmed that more covalent binding to protein occurs with BHTOH than with BHT and, in addition, BHTOH quinone methide is considerably more toxic to mouse lung epithelial cells than BHT quinone methide. These data are consistent with the hypothesis that a two-step oxidation process, i.e. hydroxylation and quinone methide formation, is required for the promotion of mouse lung tumors by BHT.
Assuntos
Hidroxitolueno Butilado , Carcinógenos/metabolismo , Indolquinonas , Indóis/metabolismo , Neoplasias Pulmonares/metabolismo , Quinonas/metabolismo , Animais , Hidroxitolueno Butilado/análogos & derivados , Hidroxitolueno Butilado/metabolismo , Hidroxitolueno Butilado/toxicidade , Testes de Carcinogenicidade , Modelos Animais de Doenças , Feminino , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Neoplasias Pulmonares/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microssomos/efeitos dos fármacos , Microssomos/metabolismo , Especificidade da Espécie , Relação Estrutura-Atividade , Uretana/toxicidadeRESUMO
Isotretinoin (13-cis retinoic acid) is frequently prescribed for severe acne [Peck, G. L., Olsen, T. G., Yoder, F. W., Strauss, J. S., Downing, D. T., Pandya, M., Butkus, D. & Arnaud-Battandier, J. (1979) N. Engl. J. Med. 300, 329-333] but can impair night vision [Fraunfelder, F. T., LaBraico, J. M. & Meyer, S. M. (1985) Am. J. Ophthalmol. 100, 534-537] shortly after the beginning of therapy [Shulman, S. R. (1989) Am. J. Public Health 79, 1565-1568]. As rod photoreceptors are responsible for night vision, we administered isotretinoin to rats to learn whether night blindness resulted from rod cell death or from rod functional impairment. High-dose isotretinoin was given daily for 2 months and produced systemic toxicity, but this caused no histological loss of rod photoreceptors, and rod-driven electroretinogram amplitudes were normal after prolonged dark adaptation. Additional studies showed, however, that even a single dose of isotretinoin slowed the recovery of rod signaling after exposure to an intense bleaching light, and that rhodopsin regeneration was markedly slowed. When only a single dose was given, rod function recovered to normal within several days. Rods and cones both showed slow recovery from bleach after isotretinoin in rats and in mice. HPLC analysis of ocular retinoids after isotretinoin and an intense bleach showed decreased levels of rhodopsin chromophore, 11-cis retinal, and the accumulation of the biosynthetic intermediates, 11-cis and all-trans retinyl esters. Isotretinoin was also found to protect rat photoreceptors from light-induced damage, suggesting that strategies of altering retinoid cycling may have therapeutic implications for some forms of retinal and macular degeneration.
Assuntos
Isotretinoína/farmacologia , Cegueira Noturna/fisiopatologia , Células Fotorreceptoras Retinianas Bastonetes/fisiopatologia , Visão Ocular/efeitos dos fármacos , Animais , Isotretinoína/administração & dosagem , Isotretinoína/uso terapêutico , Luz , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Cegueira Noturna/induzido quimicamente , Cegueira Noturna/metabolismo , Ratos , Ratos Sprague-Dawley , Células Fotorreceptoras Retinianas Cones/efeitos dos fármacos , Células Fotorreceptoras Retinianas Cones/fisiopatologia , Células Fotorreceptoras Retinianas Bastonetes/efeitos dos fármacos , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Rodopsina/biossínteseRESUMO
Two new compounds, pycnanthuquinone A (1) and pycnanthuquinone B (2), were isolated from leaves and stems of the African plant, Pycnanthus angolensis (Welw.) Warb (Myristicaceae), by bioassay-guided fractionation of an ethanolic extract using a diabetic mouse model. Pycnanthuquinones A and B are the first representatives of a novel terpenoid-type quinone skeleton, and both compounds possess significant antihyperglycemic activity.
Assuntos
Ácidos Graxos Insaturados/isolamento & purificação , Hipoglicemiantes/isolamento & purificação , Naftoquinonas/isolamento & purificação , Plantas Medicinais/química , África , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus/sangue , Diabetes Mellitus/genética , Ingestão de Alimentos/efeitos dos fármacos , Ácidos Graxos Insaturados/farmacologia , Hipoglicemiantes/farmacologia , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Naftoquinonas/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Caules de Planta/químicaRESUMO
An important consideration in improving the longevity of dental resin composite restorations is how to minimize the stresses that develop between resin composites and the wall of the preparation as the resin shrinks during polymerization. If the stress is too great, failure of the bonded interface occurs and microleakage results, with possible margin failure, staining, and secondary caries. This present project was performed to validate a previously developed FEM approach for investigating polymerization shrinkage. Light-cured resin composite was condensed into a cylindrical cavity preparation, which contained a centrally located wire. A profilometer stylus was positioned on the end of the wire to detect the initial surface displacement as the wire moved with the superficial layer of composite resin. The plots of the experimentally derived data were compared to the data plot from the FEM. The initial segments of the experimental plots matched the calculated plot very closely in shape, thus validating the FEM approach.
Assuntos
Materiais Dentários/química , Resinas Vegetais/química , Luz , Teste de Materiais/instrumentação , Teste de Materiais/métodos , Polímeros , Reprodutibilidade dos Testes , Estresse MecânicoRESUMO
In vivo bioassay-guided fractionation of the aqueous alcohol extract of the aerial parts of Teramnus labialis (Roxb.) Benth. (Fabaceae), using C57BL/Ks-db/db mice as a model for type 2 diabetes, yielded an active fraction containing a mixture of coumarins. The major coumarin present in the active fraction was identified as fraxidin.
Assuntos
Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RatosRESUMO
In vivo bioassay-guided fractionation of the aqueous alcohol extract of the aerial parts of Bidens pilosa Sch. Bip. var. radiata (Asteraceae) using C57 BL/Ks-db/db mice as a model for type 2 diabetes, yielded two known polyacetylenic glucosides, identified as 2-beta-D-glucopyranosyloxy-1-hydroxy-5(E)-tridecene-7,9,11-+ ++triyne (1) and 3-beta-D-glucopyranosyloxy-1-hydroxy-6(E)-tetradecene-8,10,1 2-triyne (2). A 3:2 mixture of compounds 1 and 2 effected a significant drop in blood glucose.
Assuntos
Asteraceae/química , Glucosídeos/isolamento & purificação , Hipoglicemiantes/isolamento & purificação , Acetileno/química , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Vegetable oils that contain fatty acids with conjugated double bonds, such as tung oil, are valuable drying agents in paints, varnishes, and inks. Although several reaction mechanisms have been proposed, little is known of the biosynthetic origin of conjugated double bonds in plant fatty acids. An expressed sequence tag (EST) approach was undertaken to characterize the enzymatic basis for the formation of the conjugated double bonds of alpha-eleostearic (18:3Delta(9cis, 11trans,13trans)) and alpha-parinaric (18:4Delta(9cis,11trans, 13trans,15cis)) acids. Approximately 3,000 ESTs were generated from cDNA libraries prepared from developing seeds of Momordica charantia and Impatiens balsamina, tissues that accumulate large amounts of alpha-eleostearic and alpha-parinaric acids, respectively. From ESTs of both species, a class of cDNAs encoding a diverged form of the Delta(12)-oleic acid desaturase was identified. Expression of full-length cDNAs for the Momordica (MomoFadX) and Impatiens (ImpFadX) enzymes in somatic soybean embryos resulted in the accumulation of alpha-eleostearic and alpha-parinaric acids, neither of which is present in untransformed soybean embryos. alpha-Eleostearic and alpha-parinaric acids together accounted for as much as 17% (wt/wt) of the total fatty acids of embryos expressing MomoFadX. These results demonstrate the ability to produce fatty acid components of high-value drying oils in transgenic plants. These findings also demonstrate a previously uncharacterized activity for Delta(12)-oleic acid desaturase-type enzymes that we have termed "conjugase."
Assuntos
Ácidos Graxos/biossíntese , Glycine max/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Primers do DNA , DNA Complementar , Etiquetas de Sequências Expressas , Ácidos Graxos Dessaturases/genética , Dados de Sequência Molecular , Plantas Geneticamente Modificadas/embriologia , Plantas Geneticamente Modificadas/enzimologia , Proteínas Recombinantes/genética , Saccharomyces cerevisiae/genética , Sementes/enzimologia , Homologia de Sequência de Aminoácidos , Glycine max/embriologia , Glycine max/enzimologiaRESUMO
Although recently developed drugs have brought significant improvement, the treatment of psychotic disorders still presents serious drawbacks. Since inherent complexity and lack of satisfactory understanding of the underlying pathophysiology impose limits for rational drug design, resourceful approaches in the search for antipsychotics are pertinent. This paper reports pharmacological properties of alstonine, a heteroyohimbine type alkaloid, which exhibited an antipsychotic-like profile, inhibiting amphetamine-induced lethality, apomorphine-induced stereotypy and potentiating barbiturate-induced sleeping time. Atypical features of alstonine were the prevention of haloperidol-induced catalepsy and lack of direct interaction with D1, D2 and 5-HT2A receptors, classically linked to antipsychotic mechanism of action.
Assuntos
Antipsicóticos/farmacologia , Plantas Medicinais , Alcaloides de Triptamina e Secologanina/farmacologia , Animais , Masculino , Camundongos , Nigéria , Sono/efeitos dos fármacosRESUMO
Lumazine synthase, which catalyzes the penultimate step of riboflavin biosynthesis, has been cloned from three higher plants (spinach, tobacco, and arabidopsis) through functional complementation of an Escherichia coli auxotroph. Whereas the three plant proteins exhibit some structural similarities to known microbial homologs, they uniquely possess N-terminal polypeptide extensions that resemble typical chloroplast transit peptides. In vitro protein import assays with intact chloroplasts and immunolocalization experiments verify that higher plant lumazine synthase is synthesized in the cytosol as a larger molecular weight precursor protein, which is post-translationally imported into chloroplasts where it is proteolytically cleaved to its mature size. The authentic spinach enzyme is estimated to constitute <0.02% of the total chloroplast protein. Recombinant "mature" spinach lumazine synthase is expressed in E. coli at levels exceeding 30% of the total soluble protein and is readily purified to homogeneity using a simple two-step procedure. Apparent V(max) and K(m) values obtained with the purified plant protein are similar to those reported for microbial lumazine synthases. Electron microscopy and hydrodynamic studies reveal that native plant lumazine synthase is a hollow capsid-like structure comprised of 60 identical 16.5-kDa subunits, resembling its icosahedral counterparts in E. coli and Bacillus subtilis.
Assuntos
Cloroplastos/enzimologia , Complexos Multienzimáticos/genética , Complexos Multienzimáticos/metabolismo , Riboflavina/biossíntese , Spinacia oleracea/enzimologia , Sequência de Aminoácidos , Arabidopsis/enzimologia , Arabidopsis/genética , Bactérias/enzimologia , Sequência de Bases , Cromatografia de Afinidade , Clonagem Molecular , Eletroforese em Gel de Poliacrilamida , Teste de Complementação Genética , Dados de Sequência Molecular , Complexos Multienzimáticos/química , Plantas Tóxicas , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/enzimologia , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Spinacia oleracea/genética , Nicotiana/enzimologia , Nicotiana/genéticaRESUMO
Although recently developed drugs have brought significant improvement, the treatment of psychotic disorders still presents serious drawbacks. Since inherent complexity and lack of satisfactory understanding of the underlying pathophysiology impose limits for rational drug design, resourceful approaches in the search for antipsychotics are pertinent. This paper reports pharmacological properties of alstonine, a heteroyohimbine type alkaloid, Which exbitited an antipsychotic-like profile, inhibiting amphetamine-induced lethaly, apomorphine-induced steotypy and potentiating barbiturate-induced slleping time. Atypical features of alstonine were the prevention of haloperidol-induced catalepsy and lack of direct interaction with D1, D2 and 5-HT2A receptors, classically linked to antipsychotic mechanism of action.
Assuntos
Animais , Masculino , Camundongos , Antipsicóticos/farmacologia , Plantas Medicinais , Alcaloides de Triptamina e Secologanina/farmacologia , Anfetamina/antagonistas & inibidores , Apomorfina/antagonistas & inibidores , Barbitúricos/antagonistas & inibidores , Estimulantes do Sistema Nervoso Central/antagonistas & inibidores , Clorpromazina/farmacologia , Clozapina/farmacologia , Diazepam/farmacologia , Eméticos/antagonistas & inibidores , Haloperidol/farmacologia , Hipnóticos e Sedativos/antagonistas & inibidores , Nigéria , Pentobarbital/farmacologia , Reserpina/farmacologia , Sono/efeitos dos fármacos , Estereotipagem , Sulpirida/farmacologiaRESUMO
Bioassay-guided fractionation of the EtOH extract of M. africana, using the in vivo noninsulin-dependent diabetes mellitus db/db mouse model, resulted in the isolation of the new daphnane-type diterpenoid maprouneacin (2). Compound 2 showed potent glucose-lowering properties when given by the oral route.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diterpenos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Animais , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , CamundongosRESUMO
Using an ethnomedical-based drug discovery program, two previously unknown compounds (SP-18904 and SP-18905) from Pycnanthus angolensis were isolated that lower glucose concentrations in mouse models of type 2 diabetes. SP-18904 and SP-18905 are terpenoid-type quinones that significantly lowered plasma glucose concentration (p <.05) when given orally to either ob/ob or db/db mice, both of which are hyperglycemic and hyperinsulinemic. The antihyperglycemic actions of SP-18904 and SP-18905 were associated with significant decreases in plasma insulin concentrations (p <.05), suggesting that both compounds lowered glucose by enhancing insulin-mediated glucose uptake. This was supported by the insulin suppression test in ob/ob mice. Studies in hyperglycemic, insulin-deficient mice and in vitro experiments on 3T3-L1 adipocytes further supported this conclusion. As such, these two terpenoid-type quinones represent a new class of compounds of potential use in the treatment of type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Naftoquinonas/farmacologia , Extratos Vegetais/farmacologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Glicemia/efeitos dos fármacos , Células Cultivadas , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Modelos Animais de Doenças , Ingestão de Alimentos/efeitos dos fármacos , Insulina/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plantas Medicinais/química , Árvores/químicaRESUMO
OBJECTIVE: A 6-month, double-blind study was undertaken to assess the efficacy and safety of a 10% carbamide peroxide gel designed for at-home tooth bleaching. METHOD AND MATERIALS: Sixty patients were randomized into two equal subgroups balanced by age, gender, and oral health status. Shade guide measurements, color transparency photographs, and colorimeter readings were taken and evaluated at baseline and 1, 2, 3, 6, 12, and 24 weeks. The active phase of treatment lasted 14 days. RESULTS: At 22 weeks postbleaching (week 24 of the study), patients receiving the active agent had a 14.1 rank order difference in the shade guide from baseline, and 66% had a clinically observable color change as determined by photographic assessment. They also had a measurable, statistically significant color change from baseline to 6 months of delta E* = 5.0. The tooth color of maxillary incisors stabilized at week 6 and maxillary canines at week 12. The mean color change lost from weeks 2 to 24 was 45% (in delta E*). Transient tissue and tooth sensitivity, noted in some patients, resolved after treatment was completed. CONCLUSION: The product tested is an effective and safe tooth-whitening agent.
Assuntos
Peróxidos/uso terapêutico , Clareamento Dental/métodos , Descoloração de Dente/terapia , Ureia/análogos & derivados , Adulto , Análise de Variância , Peróxido de Carbamida , Distribuição de Qui-Quadrado , Colorimetria , Dente Canino/química , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Géis/uso terapêutico , Humanos , Incisivo/química , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Índice Periodontal , Ureia/uso terapêuticoRESUMO
Evidence has been published that a wide array of plant-derived active principles, representing numerous classes of chemical compounds, demonstrate activity consistent with their possible use in the treatment of patients with Type 2 diabetes mellitus (DM). Despite these interesting observations, to date, metformin is the only ethical drug approved for treatment of Type 2 DM derived from a medicinal plant. Why is this so, given the fact that higher plants are such a potential source of new drugs? The answer to this rhetorical question may lie in the reliance of most pharmaceutical companies on random, in vitro, mechanism-based, high throughput screening in the initial phases of plant drug research. In this article we describe an alternative pathway to discovery of drugs for the treatment of Type 2 DM: on based on an ethnomedical approach, involving ethnobotany and traditional medicine. In particular, we present evidence that cryptolepine, an indoloquinolone alkaloid isolated from Cryptolepis sanguinolenta, significantly lowers glucose when given orally to a mouse model of diabetes. The antihyperglycaemic effect of cryptolepine leads to a significant decline in plasma insulin concentration, associated with evidence of an enhancement in insulin-mediated glucose disposal. Finally, cryptolepine increases glucose uptake by 3T3-L1 cells. These data permit us to conclude that an ethnobotanical approach to drug discovery can identify a potentially useful drug for the treatment of Type 2 DM.